The overall objectives of this proposal are to define the optimal means to diagnose early Lyme disease, to define the spectrum of cutaneous lesions which are caused by the Lyme disease spirochete, Borrelia burgdorferi, to determine the effects of antimicrobial therapy on diagnostic tests used for early Lyme disease, and to develop a predictive instrument which can be used to guide the evaluation and management of patients who present to practitioners with signs and symptoms which are suggestive of early Lyme disease. This research is designed to address the major health problem of how to diagnose and manage the large number of patients who present to practitioners in endemic areas with cutaneous lesions which are clinically and/or epidemiologically suggestive of infection by the Lyme disease spirochete. The methods used to accomplish the goals of this research include a prospective comprehensive history, physical examination, and photodocumentation of patients presenting with skin lesions suggestive of erythema migrans to practitioners in three hyperendemic foci of Lyme disease in Massachusetts and Connecticut. Diagnostic tests will include standard and novel culture techniques of blood, urine, skin biopsies, and skin aspirations antibody testing against whole Borrelia burgdorferi DNA by polymerase chain reaction using nested primers on DNA extracted from skin, blood, and urine. Using this information, we will exploit our local expertise in the development and validation of predictive instruments to develop guidelines for the diagnosis and management of this patient population.